Show simple item record

dc.contributor.authorByakwaga, Helen
dc.contributor.authorBoum II, Yap
dc.contributor.authorHuang, Yong
dc.contributor.authorMuzoora, Conrad
dc.contributor.authorKembabazi, Annet
dc.contributor.authorWeiser, Sheri D
dc.contributor.authorBennett, John
dc.contributor.authorCao, Huyen
dc.contributor.authorHaberer, Jessica E
dc.contributor.authorDeeks, Steven G
dc.contributor.authorBangsberg, David R
dc.contributor.authorMcCune, Joseph M.
dc.contributor.authorMartin, Jeffrey N
dc.contributor.authorHunt, Peter W
dc.date.accessioned2020-02-25T09:39:13Z
dc.date.available2020-02-25T09:39:13Z
dc.date.issued2014
dc.identifier.citationByakwaga, H., Boum, Y., Huang, Y., Muzoora, C., Kembabazi, A., Weiser, S. D., ... & Bangsberg, D. R. (2014). The kynurenine pathway of tryptophan catabolism, CD4+ T-cell recovery, and mortality among HIV-infected Ugandans initiating antiretroviral therapy. The Journal of infectious diseases, 210(3), 383-391.en_US
dc.identifier.urihttp://ir.must.ac.ug/xmlui/handle/123456789/512
dc.description.abstractBackground. Human immunodeficiency virus (HIV) infection–induced indoleamine 2,3-dioxygenase-1 (IDO) expression in activated monocytes and dendritic cells catabolizes tryptophan to kynurenine and other downstream catabolites that inhibit T-cell proliferation and interleukin 17 (IL-17) production. The prognostic significance of this pathway in treated HIV disease is unknown. Methods. We measured systemic IDO activity (calculated as the ratio of plasma levels of kynurenine to tryptophan; hereafter, the “KT ratio”) in HIV-infected Ugandans before and during antiretroviral therapy (ART)–mediated viral suppression and its association with the rate of subsequent CD4+ T-cell count recovery and mortality. Results. Among 435 participants, a higher pre-ART KT ratio was associated with a higher plasma virus load (P < .001) and lipopolysaccharide level (P = .018), a lower CD4+ T-cell count (P < .001), and female sex (P = .047). Through month 12 of ART-mediated viral suppression, the plasma KT ratio decreased by approximately 50% (P < .001). After adjustment for pre-ART CD4+ T-cell count, virus load, age, and sex, a higher month 12 KT ratio predicted a slower rate of subsequent CD4+ T-cell count recovery (P = .001). Thirty-nine participants died. After adjustment for pre-ART CD4+ T-cell count, virus load, body mass index, sex, and age, a higher pre-ART and month 6 KT ratio predicted increased mortality (P ≤ .016). Conclusions. The kynurenine pathway of tryptophan catabolism independently predicts poor CD4+ T-cell count recovery and increased mortality among HIV-infected Ugandans initiating ART and may be an important target for interventions.en_US
dc.description.sponsorshipThis work was supported by the National Institutes of Health (R56AI100765, R21AI078774, K24MH087227, K23MH087228, T32AA007240, R01MH054907, P30AI27763, U19 AI96109, D43 CA153717, and P01 AI076174), the Doris Duke Charitable Foundation (Clinical Scientist Development Award 2008047), and the Sullivan Family Foundationen_US
dc.language.isoenen_US
dc.publisherOxford University Pressen_US
dc.subjectTryptophanen_US
dc.subjectkynurenineen_US
dc.subjectindoleamine 2,3-dioxygenase-1en_US
dc.subjectHIVen_US
dc.subjectmortalityen_US
dc.subjectantiretroviral therapyen_US
dc.subjectUgandaen_US
dc.titleThe Kynurenine Pathway of Tryptophan Catabolism, CD4+ T-Cell Recovery, and Mortality Among HIV-Infected Ugandans Initiating Antiretroviral Therapyen_US
dc.typeArticleen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record